New Study Resuscitates Potential of Deep Brain Stimulation in Treatment-Resistant Depression

Researchers examined the role of subcallosal cingulate deep brain stimulation in treatment-resistant depression.

Deep brain stimulation (DBS) of the subcallosal cingulate white matter may be effective for the treatment of severe major depressive disorder, according to a study published in the American Journal of Psychiatry.1

The study vindicates prior work by the lead author, Helen Mayberg, MD, professor at the Icahn School of Medicine at Mount Sinai in New York, New York. In the preliminary small open-label trials of DBS of the subcallosal cingulate, patients with severe depression demonstrated response rates of 5% to 60%. However, a major multicenter randomized sham-control trial was later terminated by trial sponsor St. Jude Medical (now Abbott) given the absence of a statistically significant antidepressant response at 6 months, marking a significant setback for DBS in depression.

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The recent study, conducted by Dr Mayberg and colleagues at Emory University in Atlanta, gathered long-term outcome data for 28 patients (19 women; mean age, 45 years) who underwent DBS surgery. Eligible patients met the criteria for either a major depressive disorder or bipolar II disorder, a current depressive episode of ≥12 months, nonresponse to at least 3 antidepressant treatments, and lifetime electroconvulsive therapy. The primary outcome measure was Illness Density Index for depression based on Hamilton Depression Rating Scale scores, Global Assessment of Functioning Scale (GAF), and Clinical Global Impressions severity scale (CGI-S).

Response and remission rates were maintained at ≥50% and ≥30%, respectively, from 2 to 8 years of follow-up. All patients who underwent DBS surgery also completed at least 1 year of follow-up. Over an 8-year period, the majority of patients (71%; n=20) demonstrated consistent improvement (≥25%) from baseline depression severity ratings, with 21% of patients demonstrating continuous response to treatment from year 1.

A total of 18 patients (64%) showed improvement ≥50% from baseline for a majority of their participation time. From year 2, mean GAF score improved from an impaired baseline of 34.4±6.1 to good functioning in the 61 to 70 range; mean CGI-S increased from a severely ill baseline of 6.1±0.6 to a mildly ill score of <3 between 2 and 8 years.

“Surgical treatment of a psychiatric disorder, particularly one with permanently indwelling hardware, will necessarily be associated with more medical and surgical complications than traditional psychiatric treatments,” the authors wrote. A total of 56 serious adverse events — 19 surgery-related and 15 device-related — occurred over the course of the study, and each patient underwent 2 to 6 implantable pulse generator replacement surgeries. Overall, most patients demonstrated a robust and sustained antidepressant response to DBS treatment.

In addition, the researchers implied that DBS may require concurrent clinical care and psychopharmacologic treatment, as a majority of patients who attempted to decrease medication intake were unable to. The researchers also called for larger blinded control trials to validate the efficacy of DBS for the subcallosal cingulate, as well as qualitative studies of patients’ experiences.

Dr Mayberg stated in a Mt. Sinai press release, “the ability of DBS to support long-term maintenance of an antidepressant response and prevention of relapse is a treatment advance that can mean the difference between getting on with your life or always looking over your shoulder for your next debilitating depressive episode.”2

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


  1. Crowell AL, Riva-Posse, Holtzheimer PE, et al. Long-term outcomes of subcallosal cingulate deep brain stimulation for treatment-resistant depression [published online Oct 4, 2019]. Am J Psychiatry. doi:10.1176/appi.ajp.2019.18121427
  2. Long-term follow-up data shows deep brain stimulation is an effective treatment for treatment-resistant depression [news release]. New York, NY: Mount Sinai Health System; October 4, 2019. Accessed October 10, 2019.